Cancer Clinical Research Unit

Inclusion Criteria: - Patients with brain metastases will be included in this study. Patients with known malignancies but without brain metastases, or patients with primary brain tumors are not eligible for enrollment. - MRI confirmed 1-10 lesions. Each lesion must not be intended for resection. - No prior radiation therapy for brain tumours. - For patients enrolled to arm B, ability to tolerate RespirAct. Based on studies in patients with severe cerebrovascular disease, an 8 - 16% drop-out rate at the time of the first exposure to RespirAct CVR testing is expected [9]. The fourth generation of this device has been associated with increased tolerability secondary to elimination of a physical rebreathing circuit replaced by a digital re-breath analog. This improvement is expected to achieve a drop-out rate significantly below 10%. - Patients must have a GPA greater than or equal to 1.0. - Patients must be able to provide informed consent. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. - Patients must have sufficient fluency in English and sufficient motor and visual functioning (corrected or assisted as required) to complete the NCF-A battery. - Patients must be accessible for treatment, AE assessment and follow- up. - Limit to KPS ≥ 70 for patients in arm B; no limit for arm A - Women/men of childbearing potential must have agreed to use a highly effective contraceptive. Women of childbearing potential will have a pregnancy test to determine eligibility. Exclusion Criteria: - Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved. - Pregnant patients will be excluded from this study. - Prior cranial radiotherapy - Inability to complete MRI with contrast of the head, or a known allergy to gadolinium - Metastatic germ cell tumor, small cell carcinoma, or lymphoma or any primary brain tumor. - Patients with known malignancies but without brain metastases. - Image Findings - Widespread definitive leptomeningeal metastasis - A brain metastasis that is located ≤ 2 mm of the optic chiasm - Evidence of midline shift - Fourth ventricular narrowing, concerning for hydrocephalus - Patients who have undergone surgical resection of brain tumor are not eligible for enrollment.