3.2.1 Documentation of Disease
Pathologically (histologically or cytologically) proven diagnosis of one of the following
solid tumor malignancies within 5 years prior to registration:
• non-small cell lung cancer
• melanoma
• breast cancer
• renal cell carcinoma
• gastrointestinal cancer
If the original histologic proof of malignancy is greater than 5 years, then more recent
pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal
imaging confirmation of extracranial metastatic disease (e.g. CT of the
chest/abdomen/pelvis, PET/CT, etc.) is required.
3.2.2 Definition of Disease
• Patients must have at least 1 and up to 8 total intact brain metastases detected on a
contrast-enhanced MRI (see Appendix I for imaging guidelines) performed ≤ 21
days prior to registration.
• At least 1 of the up to 8 lesions must be a study eligible lesion, defined as lesion
with a maximum diameter as measured on any orthogonal plane (axial, sagittal,
coronal) of ≥ 1.0 cm and ≤ 3.0 cm.
• All brain metastases must be located outside of the brainstem and ≥5 mm from the
optic nerves or optic chiasm and ≤ 3.0 cm in maximum dimension.
Note: brainstem metastases per the MRI within 21 days of registration are
an exclusion criterion; however, if the MRI used for treatment planning
performed within 7 days of SRS/FSRS reveals a brainstem metastasis, the
patient remains eligible if the patient is considered an appropriate
radiosurgery candidate per the local investigator.
• Patients must have a diagnosis-specific graded prognostic assessment ≥1.5 (see
Appendix II).
• No more than 2 lesions planned for resection if clinically indicated
• No known leptomeningeal disease (LMD)
o Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined
as positive CSF cytology and/or unequivocal radiologic or clinical evidence
of leptomeningeal involvement. Patients with leptomeningeal symptoms in
the setting of leptomeningeal enhancement by imaging (MRI) would be
considered to have LMD even in the absence of positive CSF cytology. In
contrast, an asymptomatic or minimally symptomatic patient with mild or
nonspecific leptomeningeal enhancement (MRI) would not be considered
to have LMD. In that patient, CSF sampling is not required to formally
exclude LMD, but can be performed at the investigator’s discretion based
on level of clinical suspicion.
3.2.3 Age ≥ 18 years
3.2.4 Karnofsky performance status (KPS) ≥ 60
3.2.5 Not Pregnant and Not Nursing
Negative urine or serum pregnancy test (in persons of childbearing potential) within 14
days prior to registration. Childbearing potential is defined as any person who has
experienced menarche and who has not undergone surgical sterilization (hysterectomy or
bilateral oophorectomy) or who is not postmenopausal
3.2.6 Prior Treatment
No prior radiotherapy to the brain (partial or whole brain irradiation, SRS, FSRS, or
prophylactic cranial irradiation [PCI])
3.2.7 Comorbid Conditions
• New York Heart Association Functional Classification II or better (NYHA Functional
Classification III/IV are not eligible) (Note: Patients with known history or current
symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should
have a clinical risk assessment of cardiac function using the New York Heart
Association Functional Classification);
• No active infection currently requiring IV antibiotic management;
• No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
• No chronic obstructive pulmonary disease exacerbation or other acute respiratory
illness precluding study therapy;

Brainstem metastases per the MRI within 21 days of registration are
an exclusion criterion