Objective: To test whether the presence of patient- and imaging-level characteristics (1) are associated with clinically meaningful changes in mobility among patients with late-stage cancer with metastatic brain involvement, and (2) can predict their risk of near-term functional decline. Design: Prospective nested cohort study. Setting: Quaternary academic medical center. Participants: The study population consisted of a nested cohort of the patients with imaging-confirmed brain metastases (n=66) among a larger cohort of patients with late-stage lung cancer (N=311). Interventions: Not applicable. Main Outcome Measures: Functional evaluations with the Activity Measure for Post-Acute Care Computer Adaptive Test (AM-PAC-CAT) and symptom intensity ratings were collected at monthly intervals for up to 2 years. Results: In exploratory univariate models, whole brain radiation therapy (WBRT) and imaging findings of cerebellar or brainstem involvement were associated with large AM-PAC-CAT score declines reflecting worsening mobility (-4.55, SE 1.12; -2.87, SE, 1.0; and -3.14, SE 1.47, respectively). Also in univariate models, participants with new neurologic signs or symptoms at imaging (-2.48; SE.99), new brain metastases (-2.14, SE.99), or new and expanding metastases (-2.64, SE 1.14) declined significantly. Multivariate exploratory mixed logistic models, including WBRT, cerebellar/brainstem location, presence of new and expanding metastases, and worst pain intensity, had excellent predictive capabilities for AM-PAC-CAT score declines of 7.5 and 10 points (C statistics >= 0.8). Conclusions: Among patients with lung cancer and brain metastases, cerebellar/brainstem location, new and expanding metastases, and treatment with WBRT may predict severe, near-term mobility losses and indicate a need to consider rehabilitation services. (C) 2016 by the AmericanCongress of Rehabilitation Medicine