Evaluation of Neoadjuvant Stereotactic Radiosurgery (SRS) and Multi-fraction SRS Alone for the Treatment of Large Brain Metastases

Inclusion Criteria:

* Age ≥18 years.
* At least one brain metastasis appropriate for resection and not previously treated with SRS.
* Lesions ≥2.5 cm and ≤6 cm in largest dimension.
* Index lesion(s) will be treated, as outlined in the treatment section of the protocol.
* Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate Neo-SRS, i.e., the ability to lie flat in a stereotactic head mask.
* Any non-index lesion or lesions for which there is no possible resection must measure ≤4.0 cm in maximal dimension on the contrast MRI or CT brain scan obtained ≤35 days prior to pre-registration. Unresected lesions will be treated with SRS or mfSRS.
* KPS \>60
* MRI confirms 1-10 lesions, one of which one is the index lesion. Each non-index lesion (up to nine) must measure ≤4 cm in maximal extent on contrast MRI and not otherwise require resection.
* Known active or history of invasive primary non-central nervous system (CNS) cancer based on a documented histopathological diagnosis within the past three years.
* Patient can tolerate surgery and SRS.
* History/physical examination within 14 days prior to registration.
* A negative urine or serum pregnancy test (in persons of childbearing potential, defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal for at least 12 consecutive months) within ≤14 days prior to registration.
* Participants who are sexually active must agree to use medically acceptable forms of contraception during treatment during this study to prevent pregnancy.
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.

Exclusion Criteria:

* No resectable lesion ≥2.5 cm.
* Unresectable \>4 cm lesion.
* Previous whole brain irradiation.
* Progressive brain lesion treated with SRS.
* Previous resection of brain metastases.
* Leptomeningeal disease.
* Lesion diameter \>6.0 cm, or more than 20 lesions in the brain.
* Required emergency decompressive surgery for life-threatening intracranial hypertension (with a preference towards adjuvant SRS/mfSRS protocols).
* Prior diagnosis of malignant brain tumor.
* Pediatric patients (age \<18 years), pregnant women, and patients who are unable to give informed consent will be excluded.